Stringent complete remission (CR) in acute myeloid leukemia (AML) requires the absence of both morphologic and flow cytometric evidence of disease. We have previously shown that persistent AML detected by flow cytometry (FC+) before reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT) was associated with significantly increased relapse, shorter disease-free survival (DFS) and poorer overall survival (OS), independent of morphologic blast count. We evaluated the effect of FC status on outcomes of alloHCT for AML after either myeloablative conditioning (MAC) or RIC regimens. In 203 patients (MAC, n=80 and RIC, n=123) with no morphologic evidence of persistent AML pre-transplant on marrow biopsy. The allografts included 130 umbilical cord blood (UCB) and 73 sibling donors. We performed central review of pre-transplant standard sensitivity flow cytometry to identify detectable FC+. Twenty-five patients were FC+, including 15 (18.7%) receiving MAC and 10 (8.1%) RIC alloHCT. Among RIC patients FC+ was associated with significantly inferior relapse, disease-free survival (DFS), and overall survival (OS) [multiple regression hazard ratio (HR) 3.8, (95% confidence interval (95% CI) 1.7–8.7), p<0.01 for relapse; HR 2.9, (95% CI: 1.4–5.9), p<0.01 for DFS, and HR 3.4 (95%CI: 1.7–7), p<0.01 for OS]. In contrast, FC+ status was not associated with relapse or decreased OS after MAC. These data suggest that MAC, but not RIC, overcomes the negative effect of pretransplant FC+ following sibling or UCB alloHCT. Therefore, a deeper pre-transplant leukemia-free state is preferred for those treated with RIC.
Introduction Surgery is frequently required in persons with haemophilia A (PwHA). Emicizumab, a bispecific, humanized monoclonal antibody, bridges activated factor (F) IX and FX. Management of patients undergoing surgery while receiving emicizumab is of clinical interest due to paucity of data. Aim Review real‐world experience of PwHA with/without FVIII inhibitors who required surgery while receiving emicizumab prophylaxis. Methods Data regarding peri‐operative management, including type of surgery, haemostatic agent use and bleeding complications, were collected for PwHA receiving emicizumab undergoing surgery between 25/10/18 and 31/12/19 at the Indiana Hemophilia and Thrombosis Center. Analyses were exploratory and descriptive. Results Twenty minor and five major surgeries were performed in 17 and five patients, respectively. Overall, 9/20 minor surgeries were planned to occur with emicizumab as the sole haemostatic agent; of these, four required additional coagulation factor (2 due to haematomas following port removals, 1 due to oozing at port removal site, 1 due to bleeding following squamous cell carcinoma removal). Three of the 11 minor surgeries with planned additional coagulation factor resulted in non‐major bleeds; all were safely managed with additional coagulation factor. All five major surgeries were planned with additional haemostatic agents; there was 1 bleed in a patient undergoing elbow synovectomy with nerve transposition, likely triggered by physical/occupational therapy. There were no major bleeds, thrombotic events or deaths. Conclusions Additional haemostatic agent use is safe in PwHA undergoing surgery while receiving emicizumab. Additional data are needed to determine the optimal dosing/length of treatment of additional haemostatic agents to lower bleeding risk.
a trend was seen for improved survival (P 5 0.08).Our goal is to improve the nationwide survival of myeloma patients. We have established a national registry of all myeloma patients to identify areas of intervention. A population-based survey showed no difference in causes of death among patients ineligible for HDT, who died within 30 days from diagnosis as compared to patients who died between 31 and 180 days. Patients who died within 30 days had higher LDH levels and lower levels of plasma albumin as compared to those patients who died within 31-180 days, and may reflect patients with high tumor burden and a high degree of stress caused by severe infection, impaired kidney, and liver function. When compared with patients who died later than 180 days of diagnosis, WHO performance status was worse in patients with early death. A clinician will not find these results surprising. However, our data may imply that elderly patients with multiple myeloma are diagnosed with delay and a nationwide focus is now on accelerated diagnosis to clarify whether individuals presenting with an M-protein in blood or urine or with myeloma associated symptoms are suffering from myeloma. Furthermore, our survey showed that among patients with early deaths the most common causes of deaths were infections, cardiovascular failure, and renal failure. Standard induction treatment for patients ineligible for HDT now includes adjustment of chemotherapy dose according to co-morbidity and a proteasome inhibitor.Clinicians use several approaches to avoid life-threatening infections among the elderly such as granulocyte colony-stimulating factor (G-CSF) in patients with neutropenia and supportive treatment with immunoglobulins. To provide the patients with the best antibiotic treatment in future we are now conducting a nationwide prospective study on prophylactic antibiotic treatment.
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